The present invention relates to a sample separation device, in particular for high performance liquid chromatography application.
In high performance liquid chromatography (HPLC), a liquid has to be provided usually at a very well controlled flow rate (e.g. in the range of microliters to milliliters per minute) and at high pressure (typically 20-100 MPa, 200-1000 bar, and beyond up to currently 200 MPa, 2000 bar) at which compressibility of the liquid becomes noticeable. For liquid separation in an HPLC system, a mobile phase comprising a sample fluid containing compounds to be separated is driven through a stationary phase (e.g. contained in a chromatographic column), thus separating different compounds of the sample which may then be identified.
The mobile phase, for example, a solvent, is pumped under high pressure typically through a column filled with packing material, and the sample (e.g. a chemical or biological mixture) to be analyzed is injected into the column. As the sample passes through the column driven by the liquid flow, the different compounds, each one having a different affinity for the packing medium, move through the column with different velocities. Those compounds having higher affinity to the stationary phase (e.g. a packing medium) move more slowly through the column than those having lower affinity, and this velocity differences results in the compounds being separated from one another as they pass through the column.
During operation, a flow of the mobile phase, typically driven by a high pressure chromatographic pump, traverses the column filled with the stationary phase, and due to the interactions between the mobile, the stationary phase and sample components a separation of different compounds may be achieved. As a result of flow passing through the stationary phase and depending on the physical properties of the stationary phase and the mobile phase, a relatively high pressure drop takes place along the column. The composition of the mobile phase is in many cases controlled by the pump operation, as the pump provides single flows of mobile phase constituents according to the pump settings or program. These flows are then combined together to provide a mixed flow of the mobile phase or eluent. The composition and the flow rate of the mobile phase are usually precisely controlled.
In case of a leak in a fluidic supply path such as in a conduit upstream of a sample separation device, the flow and sometimes also the composition of the delivered mobile phase will be altered or disturbed, which may deteriorate proper operation of the separation system. Already minor leakages may affect the reproducibility and accuracy of the operation of the separation system. Major leaks that can lead to loss of detectable amount of liquid lead to operation stop.
JP 2005257609 discloses a liquid chromatography device intending to detect a liquid leakage in the whole system of the liquid chromatography device without using a flow sensor.
WO2009/062538, by the same applicant Agilent Technologies, discloses that in a high performance liquid chromatography system, wherein a mobile phase is driven through a stationary phase for separating compounds of a sample fluid comprised in the mobile phase, a flow rate of the mobile phase is controlled in dependence on a variation in a control value in the system.